Isradipine has good brain bioavailability and a substantially higher (>40 fold) affinity for Cav1.3 channels. The efficacy of isradipine at Cav1.2 and Cav1.3 channels is almost equal[1].

In a dose-dependent manner, isradipine (0.1~3 mg/kg; po) increases sodium excretion[3]. The striatal level of 6-hydroxydopamine-induced neurotoxicity is lessened by isradipine pretreatment. Based on data from six mice, isradipine has a dose-dependent protective effect at the striatal level. After 6-hydroxydopamine-induced degeneration, isradipine pre-treatment increases the number of surviving SNc DA cells. When intrastriatal injection of 6-hydroxydopamine is used as a slow, progressive insult, isradipine can shield SNc dopaminergic cell bodies and striatal dopaminergic terminals from it[1].

Animal/Disease Models: Rats[3]
Doses: 0.1~3 mg/kg
Route of Administration: Po
Experimental Results: Sodium excretion increased in a dose-dependent manner.

Absorption, Distribution and Excretion
Isradipine is 90%-95% absorbed and is subject to extensive first-pass metabolism, resulting in a bioavailability of about 15%-24%.
Approximately 60% to 65% of an administered dose is excreted in the urine and 25% to 30% in the feces.

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Metabolism / Metabolites
Hepatic. Completely metabolized prior to excretion and no unchanged drug is detected in the urine.

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Biological Half-Life
8 hours

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because no information is available on the use of isradipine during breastfeeding, an alternate drug may be preferred.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
95%

[1]. The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease. Neurobiol Dis. 2011;43(2):364-371.

[2]. Effects of isradipine, an L-type calcium channel blocker on permanent and transient focal cerebral ischemia in spontaneously hypertensive rats. Exp Neurol. 1997;148(1):45-50.

[3]. Selective effects of PN 200-110 (isradipine) on the peripheral circulation and the heart. Am J Cardiol. 1987;59(3):30B-36B.

Isradipine is an isopropyl ester, a methyl ester, a dihydropyridine and a benzoxadiazole.
Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. It is structurally related to felodipine, nifedipine, and nimodipine and is the most potent calcium-channel blocking agent of the DHP class. Isradipine binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and arterial smooth muscle cells. It exhibits greater selectivity towards arterial smooth muscle cells owing to alternative splicing of the alpha-1 subunit of the channel and increased prevalence of inactive channels in smooth muscle cells. Isradipine may be used to treat mild to moderate essential hypertension.
Isradipine is a Dihydropyridine Calcium Channel Blocker. The mechanism of action of isradipine is as a Calcium Channel Antagonist.
Isradipine is a second generation calcium channel blocker that is used to treat hypertension. Isradipine is associated with a low rate of serum enzyme elevations during therapy, but has not been linked convincingly to instances of clinically apparent liver injury.
Isradipine is a dihydropyridine calcium channel blockers with antihypertensive and vasodilator activities. Isradipine blocks the calcium entry through the calcium ion channels of coronary and peripheral vascular smooth muscle, thereby dilating coronary arteries and peripheral arterioles. This increases oxygen delivery due to an increased blood flow and reduces oxygen requirements due to decrease in total peripheral resistance. (NCI05)
A potent antagonist of CALCIUM CHANNELS that is highly selective for VASCULAR SMOOTH MUSCLE. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure.

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Drug Indication
For the management of mild to moderate essential hypertension. It may be used alone or concurrently with thiazide-type diuretics.

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Mechanism of Action
Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, isradipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives isradipine additional arterial selectivity. At therapeutic sub-toxic concentrations, isradipine has little effect on cardiac myocytes and conduction cells.

C19H21N3O5

371.39

371.148

75695-93-1

3784

Light yellow to yellow solid powder

1.3±0.1 g/cm3

501.9±60.0 °C at 760 mmHg

166-168°C

257.4±32.9 °C

0.0±1.3 mmHg at 25°C

1.566

3.59

1

8

6

27

685

0

HMJIYCCIJYRONP-UHFFFAOYSA-N

InChI=1S/C19H21N3O5/c1-9(2)26-19(24)15-11(4)20-10(3)14(18(23)25-5)16(15)12-7-6-8-13-17(12)22-27-21-13/h6-9,16,20H,1-5H3

3-O-methyl 5-O-propan-2-yl 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 2% DMSO +Corn oil : 10mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)